The strictly regulated microenvironment of the brain is in part maintained by the blood-brain (BBB) and blood-CSF (BCSFB) barriers. These barriers are made up of the endothelial cells of the cerebral microvasculature (BBB) and the epithelial cells of the choroid plexus (BCSFB). Both the BBB and the BCSFB control passage of ions and larger molecules into the brain by virtue of specialized transport systems, and very tight cell-to-cell connections mediated by adherens and tight junctions. It is well established that ischemic insults, such as stroke, cause a breakdown of the BBB, leading to brain edema, and this breakdown is mediated in part by alterations in tight junction and adherens junction structures. However, little is known about the cellular effects of ischemia on the BCSFB, although choroid plexus epithelial cells do express tight junction and adherens junction proteins. The hypothesis of this proposal is that the integrity of the BBB and BCFB after hypothesis and aglycemia is compromised, and that this compromise is mediated in part by the signaling effects of a rise in intracellular calcium. Calcium signaling may potentially alter the expression of tight junction, adherens junction and cytoskeletal proteins, providing a molecular mechanism for the increase in barrier permeability seen in vivo and in vitro. These studies will provide new information about the role of calcium in regulating barrier system permeability, and may provide targets for future pharmacological and therapeutic treatments of stroke.